ABSTRACT Chronic lower respiratory disease (CLRD) is the third leading cause of death globally and in the United States, and consist of chronic obstructive pulmonary disease (COPD), emphysema, chronic bronchitis, asthma and more rare entities. Both environmental factors ? such as smoking and air pollution ? and genetic factors are known to contribute to CLRD risk. However, poor understanding of the causal molecular mechanisms remains an obstacle in the path towards discovery of disease-modifying treatments for CLRD. In this project we will use ?omics data from the Multi-Ethnic Study of Atherosclerosis (MESA) ?cohort to build a map of genetic variants associating to epigenetic, transcriptomic, and metabolomics traits genome-wide. Linking these data, as well as other existing catalogs of genetic regulatory variants, to genetic associations to CLRD will elucidate molecular changes that underlie these diseases. Furthermore, we will analyze gene-environment interactions affecting genetic regulatory variants at the molecular level, and analyze its contribution to CLRD risk, analyzing the excellent CLRD phenotype data in the MESA Lung Study.